PB0711 - Increased levels of NETosis biomarkers in high-grade serous ovarian cancer patients’ biofluids: potential role in disease diagnosis and management

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

ST

Sarai Tomas-Perez

PhD Student
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
Julia Oto

Postdoctoral Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
MC

Maria Castaño

Researcher
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
CA

Cristina Aghababyan

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain; Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Presenting Author(s)

Raquel Herranz, MSc (she/her/hers)

PhD Candidate
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Co-Author(s)

AC

Aitor Cuadros-Lozano

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain; Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
EG

Eva Gonzalez-Canto

PhD Student
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
BM

Barbara Mc Cormack

Postdoctoral Researcher
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
JA

Judith Arres

MSc
Department of Statistics and Operational Research, University of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
FC

Fernando Cana

Laboratory Technician
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
LM

Laura Martinez-Fernandez

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain; Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
NS

Nuria Santonja

Medical doctor. PhD
Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
RR

Rocio Ramirez

Medical doctor
Department of Medical Oncology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
AH

Alejandro Herreros-Pomares

PhD
Gynaecological Oncology lab, Dept of Oncology, KU Leuven, Leuven, Belgium; Department of Biotechnology, Polytechnic University of Valencia, Valencia, Spain; Cancer Biomedical Research Network Center, CIBERONC, Madrid, Spain
Leuven, Vlaams-Brabant, Belgium
SC

Sarai Cañete-Mota

Medical doctor
Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain
Castellon, Comunidad Valenciana, Spain
AL

Antoni Llueca

Medical doctor. PhD
Department of Obstetrics and Gynecology, General University Hospital of Castellon, Castellón, Spain; Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellon, Castellón; Department of Medicine, University Jaume I, Castellón, Spain
Castellon, Comunidad Valenciana, Spain
MG

Martin Götte

PI
Department of Gynecology and Obstetrics, University of Münster, Germany
Münster, Nordrhein-Westfalen, Germany
JM

Josep Mari-Alexandre

Postdoctoral Researcher. Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain; Department of Pathology, General University Hospital of Valencia Consortium, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
PM

Pilar Medina

PI
Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
Valencia, Comunidad Valenciana, Spain
JG

Juan Gilabert-Estelles

Medical doctor
Research Laboratory in Biomarkers in Reproduction, Obstetrics and Gynecology, Research Foundation of the General University Hospital of Valencia, Valencia, Spain; Department of Obstetrics and Gynecology, General University Hospital of Valencia Consortium, Valencia, Spain; Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain
Valencia, Comunidad Valenciana, Spain

Background: Neutrophils are involved in cancer progression by releasing neutrophil extracellular traps (NETs). NETosis seems a pre-requisite for the establishment of omental metastases in early stages of high-grade serous ovarian cancer (HGSOC), the most lethal subtype. However, its role in advanced stages remains unknown.

Aims: To characterize a NETosis biomarker profile in biofluids from patients with advanced HGSOC.

Methods: Five biomarkers of NETosis were quantified in plasma and paired peritoneal fluid (PF) of 45 patients and 40 control women: cell-free DNA (cfDNA), nucleosomes, citrullinated histone 3 (citH3), calprotectin and myeloperoxidase (MPO) with specific kits. DNaseI activity was measured with the SRED. Finally, we created a NETosis score to assess the discriminative capacity of NETosis biomarkers between clinical groups.

Results: HGSOC patients presented a higher concentration of cfDNA, citH3 and calprotectin in plasma, and of all NETosis biomarkers in PF, than controls (Figure 1). DNaseI was not responsible for the cfDNA increase. These biomarkers showed a strong ability to differentiate both groups, mainly in PF, by means of ROC curves (Figure 2). Interestingly, neoadjuvant treatment (NT) seemed to reduce NETosis biomarkers mainly systemically (plasma) compared to the tumor environment (PF). Our NETosis score allowed to clearly differentiate HGSOC from control women with the levels of the NETosis biomarkers in PF employing a cut-off value of 23% (NETosis score >23 corresponds to HGSOC patients).

Conclusion(s): NETosis biomarkers are present in the tumor environment of advanced HGSOC patients, which might contribute to disease progression. Plasma cfDNA and calprotectin could represent minimally invasive surrogate biomarkers for HGSOC. NT modifies NETosis biomarkers mainly at the systemic level. We have developed a NETosis score that allows the discrimination of HGSOC patients from controls. ISCIII-FEDER (PI20/00075, FI21/00171, PI22/01872), GVA (ACIF/2020/216), FIHGUV Awards (2020, 2021), SETH (2020, 2021), AECC.